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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Women with recurrent hormone receptor-positive endometrial cancer who received the aromatase inhibitor anastrozole (Arimidex) experienced a clinical benefit, and reported better quality of life scores.

Note that anastrozole was well tolerated, with no unexpected or grade 3-4 toxicities, and six patients were still on treatment at an average of 20 months.

Women with recurrent hormone receptor-positive endometrial cancer who received the aromatase inhibitor anastrozole (Arimidex) experienced a clinical benefit, and reported better quality of life (QOL) scores, according to results from the international PARAGON study.

These encouraging results contrast with earlier reports that aromatase inhibitors in unselected endometrial cancer patients showed minimal activity and had an uncertain impact on QOL, they said in a poster presentation at the American Society of Clinical Oncology annual meeting in Chicago.

PARAGON, an Australian-British-Belgian trial is investigating anastrozole for seven estrogen/progesterone (ER/PR)-positive metastatic or recurrent gynecologic cancers in postmenopausal women. It involves seven individual phase II studies with the same treatment protocol using this drug, which is widely used in recurrent hormone-positive breast cancer and appears to be more active than tamoxifen in that setting.

The endometrial cancer substudy began recruiting patients from Australia, New Zealand, and the U.K. in 2011 and is now closed. The single-arm, open-label trial gave oral anastrozole 1 mg/day to 84 women with ER- and /or PR-positive hormone-naive endometrial cancer. Patients were treated until progressive disease or unacceptable toxicity. The primary endpoint was clinical benefit at 3 months defined as partial or complete response or stable disease by RECIST v1.1.

The median age of patients was 69, and 47.6% had an Eastern Cooperative Oncology Group performance status of 0, 41.7% had a status of 1, while 10.7% had a status of 2. Half had undergone no previous chemotherapy, while 34.5% had one cycle, and 15.4 % had two to three cycles.

Histologically, 64.3% of tumors were grade 1-2, and 28.6% were grade 3. Two-thirds of patients had undergone previous radiation and 33.3% had a treatment-free interval of less than 6 months.

Secondary endpoints included progression-free survival (PFS), toxicity, and QOL, the last being assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire at baseline, then monthly for the first 3 months, and then every 3 months until progression.

The investigators calculated the proportion of patients whose scores improved by at least 10-points (considered the clinically relevant threshold) for each QLQ-C30 subscale, and used linear regression to compare changes in scores between those achieving a 3-month clinical benefit and those experiencing progressive disease.

They reported that the median PFS was 3.2 months (95% CR 2.8-5.4), and the median duration of clinical benefit was 5.6 months (95% CI 3-13.7).

Anastrozole was well tolerated, with no unexpected or grade 3-4 toxicities, and six patients were still on treatment at an average of 20 months (range 13.8-25.1).

Women who experienced a 3-month clinical benefit were significantly more likely than those who progressed to experience clinically significant improvements in several QOL domains by 2 months. These included:

Emotional functioning (39% versus 6%, P=0.002)

Cognitive functioning (45% versus 19%, P=0.021)

Fatigue (47% versus 19%, P=0.015)

Global health status (42% versus 9%, P=0.003)

Clinical benefit was also associated with significantly improved mean change scores at 2 to 3 months for social functioning, financial problems, pain, appetite loss, and constipation.

In terms of pain, the 33 women who showed benefit at 3 months had a drop in mean pain score of 4.5 versus a rise in score of 13 in the 18 who progressed (P=0.008). At 2 months, those who benefited clinically had shown a drop in mean pain score of 3.9 versus an increase of 4.7 for progressors.

"We were very pleased to see that when treatment resulted in clinical benefit in terms of partial or complete response or stable disease, that benefit was associated with measurable improvements in quality of life," Mileshkin told MedPage Today.

Her group will now look at improving on these results by testing combination treatments, such as an aromatase inhibitor plus a MTOR/PI3K inhibitor or CDK 4/6 inhibitor, she said. "We also are performing a translational sub-study using archival tumor tissue from the enrolled patients to try to understand if we can pick which patients are most likely to respond," she added.

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